Researchers discover how hepatitis -B virus can exist in liver cells

Researchers have discovered a key mechanism with which hepatitis B virus (HBV) can infect and exist in liver cells, in a new study that can pave the way for potential treatments for people with chronic hepatitis -B infection.

In particular, they found that the virus infected liver cells by kidnapping protein complexes, packing the DNA to activate their own genes. With these results, the researchers were able to successfully disrupt the ability of the HBV to infect human liver cells with laboratory cultivation by infecting a connection in clinical studies as potential cancer treatment using a composite.

“Potential healing”

“If these results are confirmed by an additional study, we are optimistic that the approach can be used for the first time for the treatment of chronic infections-and therefore a potential healing could be used,” said Robert Schwartz, MD, PhD, who headed the study at Weill Cornell Medicine in New York.

The study, “A nucleosome switch Primes hepatitis B virus infection“Was published in the journal cell.

Liver inflammation in hepatitis B is caused by an infection with the hepatitis -B virus. Although HBV infections often clarify by themselves, some are chronic and last six months or more, which can lead to severe liver damage and liver cancer.

Current antiviral therapies for hepatitis B can lower the circulating mirrors of the virus, but they cannot completely prevent it from replicating its DNA.

“One of the main challenges in the treatment of hepatitis B is that the existing treatments can prevent the virus from making new copies of themselves [viral replication]But they do not fully clarify the virus from infected cells, so that the virus can exist in the liver and maintain a chronic infection, ”said Schwartz.

When HBV infected liver cells, its DNA is transported to the cell nucleus, where it forms rings of genetic material, which is called covalently closed circular DNA (CCCDNA). In combination with hosthistons or proteins that pack DNA on a coil like a thread, CCCDNA becomes a mini -romosome that serves as a template for the production of four viral proteins – C, P, S and X – that are required for HBV replication.

It is known that protein X is produced immediately after the infection to encrypt an economic complex that blocks CCCDNA as a defense mechanism against the virus. This viral protein also deteriorates of host proteins that are involved in the DNA repair, and makes infected cells more vulnerable to collect DNA errors, which ultimately leads to cancer.

However, protein X is not found in the virus and must be made from CCCDNA in newly infected liver cells.

“This raises a classic question with chicken celebrations that scientists have been confusing for decades,” said Yael David, PhD, a study that was led by the Memorial Sloan Kettering Cancer Center in New York. “How does the virus produce enough x protein to drive the viral gene? [activity] and set infection? “

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The team created model for HBV infections in vitro

To find out this, the team has created a model for an HBV infection in vitroOr under laboratory conditions outside of living organisms. Experiments confirmed that the in vitro HBV Minichromosome was very similar to how the DNA of HBV is organized in infected liver cells.

“This platform not only became a powerful tool to examine the biochemistry of the virus, but also in detail what happens in the critical first hours of an infection,” said David.

The team showed that the virus DNA has to be prepared for protein X, the viral DNA in DNA histone complexes, which are referred to as nucleosomes, such as pearls on a cord. Nucleosomes are the building blocks of chromatin, the material that forms chromosomes.

“Conventional wisdom states that the packaging of the DNA of a gene in nucleosomes blocks the ability of the cell or slows down to read this gene to make it [working] Proteins like Protein X, ”said Viviana Risca, PhD, who headed the study at Rockefeller University in New York. “But in complex organisms such as people and in the viruses that infect us, gene regulation is not always so easy. We found out [process] That leads to [working] Protein X. “

Building on these results, the researchers tested five small molecules that are known to disturb chromatin formation. They found the CBL137 molecule, an anti-cancer drug candidate that significantly suppressed the chromatin organization of the X-gene and blocked HBV replication in human liver cells in the laboratory. Remarkably, CBL137 worked in very low concentrations and influenced the virus, but no human cells.

“This made us very optimistic about the possibility of a treatment approach and at the same time prevent or limited side effects,” said David.

The researchers found that CBL137 could be helpful in the treatment of other chromatin-associated viruses such as herpes viruses, papillomaviruses and adenoviruses.

“Our results illuminate a long-term paradox and represent a potential therapeutic approach to the treatment of chronic HBV infection,” they wrote.